1. Field of the Invention
The present invention relates generally to the fields of biochemistry and medicine. In particular, the invention provides methods and compositions for treatment of therapy-resistant human breast cancer, and in particular, provides siRNA compositions that inhibit gene expression in tumor initiating cells of human breast cancer.
2. Description of Related Art
There were approximately 180,000 new cases of breast cancer diagnosed in the United States in 2007. About 15% of these, accounting for 25,000 to 30,000 cases each year, are “triple-negative breast cancer” (TNBC) in that the tumors do not express the estrogen receptor (ER), progesterone receptor (PR), or HER-2/neu (DeSantis et al., 2010). Unlike therapies targeted against steroid hormone receptors or HER2, there is no Food and Drug Administration (FDA) approved targeted drugs for the treatment of TNBC, and hence these cancers are associated with the worst prognosis. The identification of new therapeutic targets against TNBC is crucial to improving the outcome of this subtype. Use of liposome-mediated nanoparticles in order to mediate siRNA/shRNA therapy is a new approach for targeting novel non-druggable targets for which traditional therapies do not exist.
Developing therapies that are capable of attacking and destroying the “lethal seeds” driving these cancers, the “tumor initiating cells” (TICs)”, represent a significant advancement over conventional therapies.